"Guidelines for the prevention and control of legionnaire's disease in Italy": guidelines or guidance?

The creation of guidelines is a methodologically complex activity that requires technical expertise, resources and time. Methods of guideline production must meet at least these three criteria: multidisciplinarity, systematic review, and ranked recommendations. In May 2015, the new "Guidelines for the prevention and control of Legionnaire's disease" were published on the website of the Italian Ministry of Health in order to "gather, update and integrate in a single document all the previous national recommendations published". The critical review of the document has led us to conclude that this document does not comply with these three criteria, and we emphasize that guidelines should make decision-making easier, considering the various scientific approaches to a health problem and choosing the one considered most effective. Therefore, the persons responsible for the development of guidelines should strive to widely adopt and use current standards for the development of guidelines as a means to improve patient care and health outcomes.

Clinical effectiveness and safety of vildagliptin in >19 000 patients with type 2 diabetes: the GUARD study.

The present GUARD study was a prospective, non-interventional study evaluating the clinical effectiveness, safety and tolerability of vildagliptin with or without metformin in adult patients with type 2 diabetes mellitus (T2DM) studied in routine clinical practice. Patients were enrolled from countries across four geographical regions. The primary endpoint was change in glycated haemoglobin (HbA1c) concentration from baseline after 24 weeks of treatment with vildagliptin with or without metformin. Of 19 331 patients analysed, 3511 received vildagliptin and 15 820 received vildagliptin plus metformin. At week 24, the mean HbA1c was reduced significantly from baseline by -1.27% (vildagliptin: -1.17%; vildagliptin plus metformin: -1.29%; p < 0.0001). Significant reductions in HbA1c from baseline were consistently reported regardless of patient age, body mass index (BMI) or baseline HbA1c. Weight and BMI were also significantly reduced from baseline. Vildagliptin treatment with or without metformin was generally well tolerated. It provided clinically relevant glycaemic and weight control, and was well tolerated in a large multi-ethnic population of patients with T2DM studied in routine clinical practice.

Emergence of Mycobacterium gordonae in heater cooler units: a five-year prospective surveillance on devices frequently subjected to chloramine-T booster disinfection.

BACKGROUND: Worldwide, the detection of Mycobacterium chimaera in LivaNova heater-cooler units (HCUs) has led to their replacement with other HCUs, although non-tuberculous mycobacteria (NTM) have been reported also for HCUs produced by other manufacturers. In almost all hospitals of our region, LivaNova HCUs have been replaced with Maquet HCU40s, regularly disinfected with chloramine-T. AIM: To report the results of the surveillance over a 63-month operation period of the Maquet devices, and to provide a trend in NTM positivity over time. METHODS: Twenty-nine Maquet devices (HCU40 and HU35) were monitored by two culture methods and PMA-PCR method. The trend in NTM positivity rate was evaluated through the Locally Estimated Scatterplot Smoothing regression and then modelled over time through segmented logistic regression. FINDINGS: The data acquired during the study period demonstrate a remarkable increase in the positivity rate, especially after their third year (maximum slope change at 1280 days). Non-tuberculous mycobacteria were isolated in 150 water samples (37.2%); 100% and 62% of HCU40 and HU35 devices respectively were colonized with non-tuberculous mycobacteria. The most frequently detected species were Mycobacterium gordonae (73%) followed by Mycobacterium chelonae (41%) and Mycobacterium paragordonae (11%). CONCLUSION: Preventive strategies by disinfection with chloramine-T did not effectively reduce non-tuberculous mycobacteria colonization of Maquet devices. Although, to date, no cases of post-operative invasive infections linked to Maquet devices have been reported, our microbiological results emphasize the need for 1) designing changes to increase safety of devices and 2) researching and developing new disinfection protocols including alternative molecules.

The effect of vildagliptin relative to sulphonylureas in Muslim patients with type 2 diabetes fasting during Ramadan: the VIRTUE study.

AIMS: To assess, in a real-world setting, the effect of vildagliptin compared with sulphonylurea (SU) treatment on hypoglycaemia in Muslim patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan. METHODS: This multinational, non-interventional study, conducted in Asia and the Middle East, included Muslim adult patients with T2DM who received treatment with vildagliptin or SU as add-on to metformin or monotherapy. During a ~16-week observation period, data were collected up to 6 weeks before and 6 weeks after Ramadan fasting. The primary study objective was to compare the proportion of patients with ≥ 1 hypoglycaemic event (HE) during fasting. RESULTS: Of > 1300 patients enrolled in the study, 684 were treated with vildagliptin and 631 with SUs. Significantly fewer patients experienced ≥ 1 HE with vildagliptin compared with those receiving SUs (5.4% vs. 19.8%, respectively; p < 0.001); no vildagliptin-treated patients reported a grade 2 HE, vs. 4 SU-treated patients (p = 0.053). Mean HbA1c changes from baseline were vildagliptin: -0.24%, SUs: +0.02% (p < 0.001). Mean body weight reductions from baseline were vildagliptin: -0.76 kg, SUs: -0.13 kg (p < 0.001). A higher proportion of SU-treated patients experienced adverse events (AEs) compared with vildagliptin (22.8% vs. 10.2%). This difference was driven by hypoglycaemia as the most common AE. CONCLUSIONS: In this real-world study of fasting Muslim patients with T2DM, vildagliptin was associated with significantly fewer hypoglycaemic episodes compared with SU therapy. This outcome is particularly meaningful when viewed in the context of good glycaemic and weight control observed in vildagliptin-treated patients. Vildagliptin was well tolerated in this patient population.

Evaluation of the usefulness of a new direct immunofluorescence assay (ScanVIT-Legionella) for monitoring hospital water systems contaminated with Legionella spp.

AIMS: To compare the efficiency of the ScanVIT-Legionella test (Vermicon, Munich, Germany) vs a conventional culture method for the quantification of Legionella spp. in hospital water samples in daily hospital practice. METHODS AND RESULTS: The detection of Legionella spp. takes place on a cultivated filter brought into contact with dye-marked gene probes. The results are analysed under fluorescence microscopy. Bacteria that light up green belong to the genus Legionella; those that light up both green and red belong to the species Legionella pneumophila. Our results showed that the ScanVIT test has a sensitivity of 90%; agreement between the two methods was 82%. In the 48 samples that tested positive with both methods, the Legionella concentration detected by the culture method was consistently higher. A statistically significant difference between the results obtained with the two test methods emerged at the Wilcoxon test (P < 0.001). CONCLUSION: The ScanVIT test may be recommended for investigating the presence of Legionella by qualitative testing. SIGNIFICANCE AND IMPACT OF THE STUDY: Given the simplicity of colony identification by fluorescence, the ScanVIT test can be used in laboratories where staffs are not experienced in identifying typical colonies of Legionella.

Failure to eradicate non-tuberculous mycobacteria upon disinfection of heater-cooler units: results of a microbiological investigation in northwestern Italy.

BACKGROUND: Heater-cooler units (HCUs) used during cardiopulmonary bypass may become colonized with non-tuberculous mycobacteria (NTM), including Mycobacterium chimaera. Recently, a worldwide investigation conducted in hospitalized infected patients has detected M. chimaera in several Stockert 3T HCUs manufactured by LivaNova. AIM: Microbiological surveillance on Stockert 3T (LivaNova) and Maquet HCU40 (Getinge) devices as well as an evaluation of the efficacy of their recommended decontamination protocols. METHODS: A total of 308 water samples were collected from 29 HCUs: 264 samples were collected from 17 Stockert 3T HCUs and 44 samples from 12 Maquet HCU40 devices. Samples were tested for total viable counts (TVCs) at both 22 and 36°C, Pseudomonas aeruginosa, coliform bacteria, and NTM. The microbiological surveillance began in June 2017 and ran until October 2019. FINDINGS: A total of 308 HCU water samples were analysed, 65.5% of which yielded NTM. The most frequently colonized device with NTM was the Stockert 3T (88.2%), with a frequency of positive samples of 59.5% (157/264). The Maquet HCU40 devices less frequently yielded NTM (33.3%), with a frequency of positive water samples of 13.6% (6/44). Disinfection procedures were effective in reducing TVCs of bacteria with the exception of NTM species. NTM were detected in both pre-disinfection (50.1%) and post-disinfection (55.7%) samples, and no significant association was found between disinfection and NTM results both in Stockert 3T and Maquet HCU40 devices. CONCLUSION: This study suggests that manufacturers' procedures for disinfection are ineffective and/or inadequate. Until effective disinfection protocols become available, the only way to minimize the risk of NTM contamination is to closely monitor the water quality in the HCU, keep it as clean as possible, and treat it like any other biohazardous material.

Reduction of turnaround time for non-tuberculous mycobacteria detection in heater-cooler units by propidium monoazide-real-time polymerase chain reaction.

BACKGROUND: Invasive non-tuberculous mycobacteria (NTM) infections are emerging worldwide in patients undergoing open-chest cardiac bypass surgery exposed to contaminated heater-cooler units (HCUs). Although this outbreak has been investigated by culturing bacteria isolated from HCU aerosol and water samples, these conventional methods have low-analytic sensitivity, high rates of sample contamination, and long turnaround time. AIM: To develop a simple and effective method to detect NTM in HCUs by real-time polymerase chain reaction (PCR), with a short laboratory turnaround time and reliable culture results. METHODS: A total of 281 water samples collected from various HCUs at seven Italian hospitals were simultaneously screened for NTM by a propidium monoazide (PMA)-PCR assay and by conventional culture testing. The results were analysed with culture testing as the reference method. FINDINGS: (i) The agreement between culture testing and PMA-PCR was 85.0% with a cycle threshold (CT) cut-off value of <38 vs 80.0% with a CT of <43, with a moderate Cohen's κ-coefficient; (ii) the CT cut-off value of <42 was deemed more suitable for predicting positive specimens; (iii) given the low concentration of target DNA in water samples, the minimum volume to be tested was 1 L. CONCLUSION: The use of PMA-PCR for fast detection of NTM from environmental samples is highly recommended in order to ascertain whether HCUs may represent a potential source of human exposure to NTM. This reliable and simple method reduces laboratory turnaround time compared to conventional methods (one to two days vs eight weeks, respectively), thereby improving control strategies and effective management of HCUs.

Prevalence of anti-legionella antibodies among Italian hospital workers.

This study evaluated the prevalence of anti-legionella antibodies in workers at hospitals with a long-term history of legionella contamination. The hospitals are located in Milan and Turin, northern Italy, and in Naples and Bari, southern Italy. Antibody prevalence and titres of healthcare workers, medical and dental students and blood donors were assessed. In total 28.5% of subjects were antibody positive, most frequently to L. pneumophila serogroups 7-14. Major differences were observed in seroprevalence and type of legionella antibody in persons from different geographic areas. Healthcare workers had a significantly higher frequency of antibodies compared with blood donors in Milan (35.4 vs 15.9%, P<0.001), whereas in Naples both groups exhibited high antibody frequency (48.8 vs 44.0%) and had a higher proportion of antibodies to legionella serogroups 1-6. Dental workers had a higher seroprevalence than office staff in Bari, but not in Turin, where daily disinfecting procedures had been adopted to avoid contamination of dental unit water. No association was found between the presence of antibodies and the presence of risk factors for legionellosis, nor with the occurrence of pneumonia and/or flu-like symptoms. In conclusion, the presence of legionella antibodies may be associated with occupational exposure in the hospital environment, but there was no evidence of any association with disease.

Antibody detection and cross-reactivity among species and serogroups of Legionella by indirect immunofluorescence test.

The purpose of the present study was to determine possible cross-reactivity between different serogroups or between different species by means of bacterial smears of individual L. pneumophila serogroups and several non-pneumophila Legionella spp. Using BIOCHIP slide we found a considerable frequency of cross-reactions with L. pneumophila serogroup 12 (88.4%) therefore BIOCHIP slide proved as useful method for identification of cross-reactivity between members of the Legionnellaceae.

[Immunogenicity of a recombinant vaccine against viral hepatitis B]. / Analisi dell'immunogenicità di un vaccino recombinante anti-epatite virale di tipo B.

The introduction in Italy of recombinant DNA hepatitis B vaccines has allowed to plan out a very important programme of vaccination; in Italy the compulsory vaccination against hepatitis B virus begun from 1991. Because of the reduction of vaccine cost, the screening for serum markers of HBV infection is needless. On the contrary, the test of antiHBs titres after the vaccination is important in order to take into account a booster vaccine dose and to carry out revaccination strategies. In this study, we analyzed 419 subjects vaccinated with Engerix-B; the immune response was correlated with private and behaviour data.

[Cost analysis of toxoplasma infection control in pregnancy]. / Analisi dei costi relativi al controllo dell'infezione toxoplasmica in corso di gravidanza.

In Italy, the management of Toxoplasma infection screening in pregnant women is often unproductive and inefficient and generates a wide variability of costs. This study evaluated performance parameters in the screening management of a population of pregnant women, estimated its costs and compared them with the costs of a full application of Ministerial Documents of 1995 and 1998. We controlled until delivery 830 pregnant women who had done the first blood test between September 1st and December 31st 1997. The costs of direct and indirect testing were analysed using the Excel database and statistical software package. Of the 573 pregnant women defined 'susceptible' at the first test, only 240 (42%) did further blood tests during the II and III trimesters, 30% did no more tests and the remaining women adopted a heterogeneous behaviour. The mean cost of each screening was found to be euro 54.47/pregnancy and euro 60.05/pregnancy with a full application of the Ministerial Document of 1995. A full application of Ministerial Document of 1998, instead, would have involved a cost of euro 94.28/pregnancy for 5 tests, euro 111.40/pregnancy for 6 tests and euro 128.51 for 7 tests. The study shows that the management of toxoplasmosis screening during pregnancy needs greater attention to the prescription of tests, so that useless testing can be reduced and the efficacy of the screening improved, two important goals the Ministerial Documents were designed to achieve.

Compulsory and non-compulsory immunizations: contraindications perceived by medical practitioners.

A total of 284 general practitioners (GPs), paediatricians and doctors of public vaccination centres (DPVC) were interviewed to investigate their willingness to immunize children with compulsory (diphtheria-tetanus, oral polio) and non-compulsory (measles, pertussis) vaccines in the presence of 19 different medical histories. We observed a reluctance to immunize in the case of false contraindications, a lack of information mainly about non-compulsory immunizations, and doubts about the real contraindications to polio, measles and pertussis vaccines. The frequency of correct answers to the question posed was significantly higher in the group with less than 20 years of experience, and the DPVCs proved better informed about immunization. However, the crucial role played by the GPs and paediatricians' advice can prejudice the correct use of active immunization.